Polymorphisms in CYP1B1, GSTM1, GSTT1 and GSTP1, and susceptibility to breast cancer

Beth O. Van Emburgh, Jennifer J. Hu, Edward A. Levine, Libyadda J. Mosley, Nancy D. Perrier, Rita I. Freimanis, Glenn O. Allen, Peter Rubin, Gary B. Sherrill, Cindy S. Shaw, Lisa A. Carey, Lynda R. Sawyer, Mark Steven Miller

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Polymorphisms in the cytochrome P450 1B1 (CYP1B1) and glutathione S-transferase (GST) drug metabolic enzymes, which are responsible for metabolic activation/ detoxification of estrogen and environmental carcinogens, were analyzed for their association with breast cancer risk in 541 cases and 635 controls from a North Carolina population. Each polymorphism, altering the catalytic function of their respective enzymes, was analyzed in Caucasian and African-American women. As reported in previous studies, individual polymorphisms did not significantly impact breast cancer risk in either Caucasian or African-American women. However, African-American women exhibited a trend towards a protective effect when they had at least one CYP1B1 119S allele (OR=0.53; 95% CI=0.20-1.40) and increased risk for those women harboring at least one CYP1B1 432V allele (OR=5.52; 95% CI=0.50-61.37). Stratified analyses demonstrated significant interactions in younger (age ≤560) Caucasian women with the CYP1B1 119SS genotype (OR=3.09; 95 % Cl= 1.22-7.84) and younger African-American women with the GSTT1 null genotype (OR=4.07; 95% Cl=1.12-14.80). A notable trend was also found in Caucasian women with a history of smoking and at least one valine allele at GSTP1 114 (OR=2.12; 95% CI=1.02-4.41). In Caucasian women, the combined GSTP1 1051V/VV and CYP1B1 119AA genotypes resulted in a near 2-fold increase in risk (OR=1.96; 95% CI=1.04-3.72) and the three way combination of GSTP1 105IV/VV, CYP1B1 119AS/SS and GSTT1 null genotypes resulted in an almost 4-fold increase in risk (OR=3.97; 95% CI=1.27-12.40). These results suggest the importance of estrogen/ carcinogen metabolic enzymes in the etiology of breast cancer, especially in women before the age of 60, as well as preventative measures such as smoking cessation.

Original languageEnglish (US)
Pages (from-to)1311-1321
Number of pages11
JournalOncology Reports
Volume19
Issue number5
DOIs
StatePublished - May 2008

Keywords

  • Breast neoplasms
  • Cytochrome P450
  • Glutathione S-transferase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Polymorphisms in CYP1B1, GSTM1, GSTT1 and GSTP1, and susceptibility to breast cancer'. Together they form a unique fingerprint.

  • Cite this

    Van Emburgh, B. O., Hu, J. J., Levine, E. A., Mosley, L. J., Perrier, N. D., Freimanis, R. I., Allen, G. O., Rubin, P., Sherrill, G. B., Shaw, C. S., Carey, L. A., Sawyer, L. R., & Miller, M. S. (2008). Polymorphisms in CYP1B1, GSTM1, GSTT1 and GSTP1, and susceptibility to breast cancer. Oncology Reports, 19(5), 1311-1321. https://doi.org/10.3892/or.19.5.1311